title: Developmental androgen excess disrupts reproduction and energy homeostasis in adult male mice.
abstract: Polycystic ovary syndrome is a common endocrine disorder in females of reproductive age and is believed to have a developmental origin in which gestational androgenization programs reproductive and metabolic abnormalities in offspring. During gestation, both male and female fetuses are exposed to potential androgen excess. In this study, we determined the consequences of developmental androgenization in male mice exposed to neonatal testosterone (NTM). Adult NTM displayed hypogonadotropic hypogonadism with decreased serum testosterone and gonadotropin concentrations. Hypothalamic KiSS1 neurons are believed to be critical to the onset of puberty and are the target of leptin. Adult NTM exhibited lower hypothalamic Kiss1 expression and a failure of leptin to upregulate Kiss1 expression. NTM displayed an early reduction in lean mass, decreased locomotor activity, and decreased energy expenditure. They displayed a delayed increase in subcutaneous white adipose tissue amounts. Thus, excessive neonatal androgenization disrupts reproduction and energy homeostasis and predisposes to hypogonadism and obesity in adult male mice.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine and Comprehensive Center on Obesity, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA Division of Endocrinology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112-2632, USA Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA INSERM U1048, Institute of Metabolic and Cardiovascular Diseases of Rangueil, Toulouse 31432, France.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Nohara
authors.forename: Suhuan
authors.initials: S
authors.lastname: Liu
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Meyers
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ferron
authors.forename: Gérard
authors.initials: G
authors.lastname: Karsenty
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000728:Androgens / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D006062:Gonadotropins / Q000097:blood; D007006:Hypogonadism / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007248:Infertility, Male / Q000209:etiology; D059648:Kisspeptins / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood / Q000633:toxicity
chemical_list: D000728:Androgens; D004785:Environmental Pollutants; D006062:Gonadotropins; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D009419:Nerve Tissue Proteins; D013739:Testosterone; C004648:testosterone enanthate
keywords: androgens; energy homeostasis; reproduction